超敏反應英五班課件

TheBigBangTheoryTheBigBangTheory1

Hypersensitivity（allergy）

Hypersensitivityisaninappropriateimmuneresponse,whichisheightenedreactivitytoanantigen,suchresponseleadtotissuedamage,immunopathology.ThevarioushypersensitivitystateswereclassifiedintoIthroughIVtypesbyGellandCoombs.TypeI,IIandIIIreactionsaremediatedbyantibodies,whereastypeIVreactionsaremediatedbyTcells.Hypersensitivity（allerg2I.TypeIhypersensitivity（anaphylaxis）Themajorcomponents

（1）allergen

drug,chemical

inhalantallergen：pollens、Dustmitefoodallergens：nuts,seafood

I.TypeIhypersensitivity（ana3PlanetreePlanetree4Castor-oilplantCastor-oilplant5DustmiteDustmite6（2）IgEantibodyandIgEreceptorTh2Igheavychainisotypeswitching（2）IgEantibodyandIgErecep7(2)anaphylacticshockcausedbyanimalserum（TAT）(4)hypersensitivityreactioningastrointestinaltractBiologicalactivemediators：Hygienehypothesis:Theremarkableincreaseinasthmaprevalencethathasoccurredoverthelasttwodecadesisthoughttobecausedbychangesintheenvironmentduetoimprovedhygieneandfewerchildhoodinfection.furproteinEssay

DiscussONEofthefollowingstatementsCommondiseasescausedbytypeIIIhypersensitivityHygienehypothesisepithelialIgE----FcRI(ITAM)epithelialMastcell/basophils:FcεRIallergenenterthebodystimulateAg-specificBcellsdifferentiatedtoplasmacellsproductionofIgESerumsicknessPFER:peakexpiratoryflowrateepithelialTheremarkableincreaseinasthmaprevalencethathasoccurredoverthelasttwodecadesisthoughttobecausedbychangesintheenvironmentduetoimprovedhygieneandfewerchildhoodinfection.PFER:peakexpiratoryflowratepurifiedproteinderivative(PPD),aproteinAgofmycobacteriumtuberculosis,elicitsaDTHreaction,calledtuberculinreaction.PoststreptococcalglomerulonephritisLevelsofIgEandatopicdiseases(2)anaphylacticshockcaused8IgE

andIgEreceptorsIgE----Fc

RI(ITAM)

AntigenindirectlycrosslinksFc

R

onmastcellsorbasophils?IgEandIgEreceptorsAntige9（3）CellsMastcell/basophils:FcεRIeosinophils：expressFcεRIafterstimulationofIL-5，MCP-3CrosslinkDegranulationReleaseofpreformedmediatorsandnewlyproducedmediators（3）CellsMastcell/basophils:10超敏反應英五班課件11LightphotomicrographandElectronmicrographofMastcellactivationAbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaundersLightphotomicrographandElec122.MechanismofTypeIhypersensitivitySensitizationphase

ExcitationphaseEffectorphase

2.MechanismofTypeIhyperse131.Sensitizationphaseallergenenterthebody

stimulateAg-specificBcellsdifferentiatedtoplasmacells

productionofIgEBindwith

high-affinityFc

RIwhichexpressedbymastcellsandbasophilsActivatedmastcelloractivatedbasophil1.SensitizationphaseActivate142.ExcitationphaseThesameallergenenterthebodyagain→bindtoIgEwhichwasboundtomastcellsand/orbasophils,crosslinkofFc

RI→inductionthedegranuationofmastcellsandbasophils,releasebiologicalactivemediators2.Excitationphase15Biologicalactivemediators：

1.preformedmediators：histamine,eosinophilchemotacticfactor(ECF),kininogenase,tryptase

2.newlyproducedmediators:leukotrienes,prostaglandinD2,plateletactivatingfactor,cytokinesBiologicalactivemediators：163.Effectorphase

Immediatephase—severalsecondsaftercontactofallergen,canpersistseveralhours,causedbyhistamineLatephase—6-12haftercontactofallergen,canpersistseveraldays3.Effectorphase17Distributionandfunctionofhistaminetypeoftissue

effect

clinical

receptor

contraction

relaxationmanifestationH1airwaysmoothmuscles

+asthma

alimentarytractmuscles+diarrhea,vomit

vascularendothelialcell+edema

H2vascularsmoothmuscle+shockDistributionandfunctionofh18AbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaundersBiologiceffectsofmediatorsofimmediatehypersenitivityAbulK.abbasetal.Cellular19DifferentsubstancescrosslinkFcRDifferentsubstancescrosslin203.IgEmediatedallerigicdiseases(typeIhypersensitivity)(1)anaphylacticshockcausedbydrugs(2)anaphylacticshockcausedbyanimalserum（TAT）(3)hypersensitivityreactioninrespiratorytract

allerigicrhinitis,bronchialasthma3.IgEmediatedallerigicdis21drug,chemicalDistributionandfunctionofhistamineHygienehypothesis(2)anaphylacticshockcausedbyanimalserum（TAT）PrincipalsofpreventionandtherapyfortypeIhypersensitivity(4)hypersensitivityreactioningastrointestinaltractDegranulationHygienehypothesisinfection:changedepitopeAntigenindirectlycrosslinksFcR

onmastcellsorbasophils?cellsurfaceAg→Ab（IgG）(1)anaphylacticshockcausedbydrugsWhat’stheroleofTh17andIL-17Ainasthmaandrhinitis?HygienehypothesisHypersensitivityisaninappropriateimmuneresponse,whichisheightenedreactivitytoanantigen,suchresponseleadtotissuedamage,immunopathology.largeimmunecomplexes-----phagocytosisIgE----FcRI(ITAM)EffectorphasePFER:peakexpiratoryflowrate（cellmediated,delayedtype）Activatedmastcelloractivatedbasophil(5)hypersensitivityreactioninskin(4)hypersensitivityreactioningastrointestinaltract

seafood,milkBeestingurticariadrug,chemical(5)hypersensi22超敏反應英五班課件23Allergicreactioninresponsetotestantigenscanbedividedintoanimmediateresponseandalate-phaseresponseAsthmaticresponseinthelungswithnarrowingoftheairwaysPFER:peakexpiratoryflowrateAllergicreactioninresponse244.PrincipalsofpreventionandtherapyfortypeIhypersensitivity4.Principalsofpreventiona25（1）Skintest（1）Skintest26（2）DesensitizationtherapyHeteroserumdesensitization：smalldose,repeatedinjection,

30-50mininterval（TAT）allergictopenicillinisforbiddentousethismethodSpecificallergendesensitization：smalldose,repeatedinjection,

longtimeinterval,inducingIgGproduction，decreasingIgEproduction超敏反應英五班課件27（3)Drugtherapy（3)Drugtherapy28IgE----FcRI(ITAM)(2)anaphylacticshockcausedbyanimalserum（TAT）farmer'slungAllergicreactioninresponsetotestantigenscanbedividedintoanimmediateresponseandalate-phaseresponseepithelialPFER:peakexpiratoryflowrate（cellmediated,delayedtype）CommondiseasescausedbytypeIVhypersensitivityDegranulationdrug:hapten（1）transfusionreactionseosinophils：expressFcεRIafterstimulationofIL-5，MCP-3receptorcontractionrelaxationmanifestationMechanismofTypeIhypersensitivityallergenenterthebodystimulateAg-specificBcellsdifferentiatedtoplasmacellsproductionofIgE（2）HemolyticdiseaseofthenewborninducedbyRhesusincompatibility1903ArthusArthusreaction,arthus-likereactionIgE----FcRI(ITAM)Hypersensitivityisaninappropriateimmuneresponse,whichisheightenedreactivitytoanantigen,suchresponseleadtotissuedamage,immunopathology.Heteroserumdesensitization：smalldose,repeatedinjection,30-50mininterval（TAT）HygienehypothesisTheremarkableincreaseinasthmaprevalencethathasoccurredoverthelasttwodecadesisthoughttobecausedbychangesintheenvironmentduetoimprovedhygieneandfewerchildhoodinfection.IgE----FcRI(ITAM)Hygienehy29II.TypeIIhypersensitivity（cytotoxichypersensitivity）

II.TypeIIhypersensitivity30MechanismoftypeIIhypersensitivity（1）Ag

cellsurfaceAg→Ab（IgG）MechanismoftypeIIhypersens31（2）specificAb,complementandeffectorcell

ADCC、CDC、phagocytosis（2）specificAb,complementan32超敏反應英五班課件332.CommondiseasescausedbytypeIIhypersensitivity（1）transfusionreactionsBloodtype

Ag Ab/serumA A anti-BB B anti-AAB A、B noneO H anti-A、anti-B2.Commondiseasescausedbyt34LevelsofIgEandatopicdiseasesseafood,milkCellularandMolecularImmunology,7thedition,ElsevierSaundersTypeIhypersensitivity（anaphylaxis）MechanismofTypeIhypersensitivityHygienehypothesis(1)anaphylacticshockcausedbydrugsabbasetal.receptorcontractionrelaxationmanifestationB B anti-AInhaledantigeninducedtypeIIIhypersensitivityImmediatephase—severalsecondsaftercontactofallergen,canpersistseveralhours,causedbyhistamineMechanismofTypeIhypersensitivity（1）Infectivehypersensitivityfurprotein(2)anaphylacticshockcausedbyanimalserum（TAT）drug:haptenTheinhalationofallergensleadstohyperreactivity,recruitmentofeosinophils,mastcells,andlymphocytesintheupperandlowerairwaystriggeringtheinflammatorycascadeandgeneratinglocalandsystemicinflammatoryresponses.IgEmediatedallerigicdiseases(typeIhypersensitivity)（2）HemolyticdiseaseofthenewborninducedbyRhesusincompatibilityLevelsofIgEandatopicdise35（3）Autoimmunehemolyticanemiainfection:changedepitopedrug:hapten

（3）Autoimmunehemolyticanemia36（4）Gravesdisease(specialtype)

ThyroidepithelialcellTSH-RTSHT3、T4Anti-TSH-RAb（4）Gravesdisease(specialtyp37超敏反應英五班課件38超敏反應英五班課件39III.TypeIIIhypersensitivity（solubleimmunecomplex）

MechanismoftypeIIIhypersensitivity

largeimmunecomplexes-----phagocytosis

smallimmunecomplexes-----kidneyfiltration

medieum

immunecomplexes-----existforalongtime,depositinsmallvesselsIII.TypeIIIhypersensitivit40超敏反應英五班課件412.CommondiseasescausedbytypeIIIhypersensitivity（1）localimmunecomplex-mediateddiseases

1903ArthusArthus

reaction,arthus-likereaction

2.Commondiseasescausedby42InhaledantigeninducedtypeIIIhypersensitivityDiseasesantigen

haydustfarmer'slung

furproteinfurrier'slung

pigeondroppingspigeon-fancier'sdisease

Penicilliumcaseisporescheesewasher'sdisease

Hiddenmoldsporesmaplebarkstripper'sdiseaseInhaledantigeninducedtypeI43（2）Systemicimmunecomplex-mediateddiseases

SerumsicknessPoststreptococcalglomerulonephritisRheumatoidarthritisSystemiclupuserythematosus

（2）Systemicimmunecomplex-me44(2)anaphylacticshockcausedbyanimalserum（TAT）CommondiseasescausedbytypeIIIhypersensitivityEffectorphaseActivatedmastcelloractivatedbasophil(2)anaphylacticshockcausedbyanimalserum（TAT）(1)anaphylacticshockcausedbydrugsPFER:peakexpiratoryflowratetypeoftissueeffectclinical（cellmediated,delayedtype）CommondiseasescausedbytypeIIIhypersensitivityMechanismofhypersensitivityreactionoffourtypesabbasetal.Hygienehypothesis:Theremarkableincreaseinasthmaprevalencethathasoccurredoverthelasttwodecadesisthoughttobecausedbychangesintheenvironmentduetoimprovedhygieneandfewerchildhoodinfection.Hygienehypothesis:Theremarkableincreaseinasthmaprevalencethathasoccurredoverthelasttwodecadesisthoughttobecausedbychangesintheenvironmentduetoimprovedhygieneandfewerchildhoodinfection.newlyproducedmediators:leukotrienes,prostaglandinD2,plateletactivatingfactor,cytokinesDegranulation(2)anaphylacticshockcausedbyanimalserum（TAT）（2）specificAb,complementandeffectorcellADCC、CDC、phagocytosis（solubleimmunecomplex）Serumsickness(2)anaphylacticshockcaused45超敏反應英五班課件46超敏反應英五班課件47IV.TypeIV

hypersensitivity（cellmediated,delayedtype）

MechanismoftypeIVhypersensitivityAg→effectorcellInflammationandcytotoxicityTh1TcIV.TypeIVhypersensitivityMe48超敏反應英五班課件492.CommondiseasescausedbytypeIVhypersensitivity（1）Infectivehypersensitivity

Leprosy

2.Commondiseasescausedby50TuberculosisAbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaundersTuberculosisAbulK.abbaseta51Contactdermatitiscausedbyivyprison（2）

ContactdermatitisContactdermatitiscausedbyi52AbulK.abbasetal.CellularandMolecularImmunology,7thedition,ElsevierSaundersExample：purifiedproteinderivative(PPD),aproteinAgofmycobacteriumtuberculosis,elicitsaDTHreaction,calledtuberculinreaction.Positiveskintestresponseisclinicalindicatorforevidenceofpreviousoractivetuberculosisinfection.AbulK.abbasetal.Cellular53超敏反應英五班課件54Keypoints：DefinitionofhypersensitivityreactionsMechanismofhypersensitivityreactionoffourtypesRelateddiseasesKeypoints：55Essay

DiscussONEofthefollowingstatementsHygienehypothesis:Theremarkableincreaseinasthmaprevalencethathasoccurredoverthelasttwodecadesisthoughttobecausedbychangesintheenvironmentduetoimprovedhygieneandfewerchildhoodinfection.Essay

DiscussONEofthefoll56Allergicdiseases,includingrhinitisandasthma,arechronicinflammatorydisorderswithaprevailingTh2immuneresponse.Theinhalationofallergensleadstohyperreactivity,recruitmentofeosinophils,mastcells,andlymphocytesintheupperandlowerairwaystriggeringtheinflammatorycascadeandgeneratinglocalandsystemicinflammatoryresponses.Th17cellsandIL-17Aplayaroleinthedevelopmentandprogressionofallergicdiseases.PharmacologicaltreatmentmightrestorethebalancebetweenTh17andTregpromotingtheresolutionofinflammationinairwaydiseases.What’stheroleofTh17andIL-17Ainasthmaandrhinitis?What’stheroleofTh17andIL57超敏反應英五班課件58PlanetreePlanetree592.MechanismofTypeIhypersensitivitySensitizationphase

ExcitationphaseEffectorphase

2.MechanismofTypeIhyperse6